What Is Cirrhosis?
Cirrhosis is defined by diffuse hepatic fibrosis and nodule formation, disrupting normal liver architecture. It results from sustained hepatic injury across a range of etiologies: chronic viral hepatitis, alcohol-related liver disease, MASLD, autoimmune hepatitis, cholestatic diseases (PBC, PSC), and others.
Cirrhosis is broadly classified as compensated (no prior decompensation; 10-year survival ~80%) or decompensated (presence of ascites, variceal hemorrhage, hepatic encephalopathy, or jaundice; median survival ~2 years without transplantation).
Portal Hypertension: The Central Mechanism
Most complications of cirrhosis arise from portal hypertension — elevated pressure in the portal venous system due to increased vascular resistance from fibrosis and dynamic vasoconstriction. The hepatic venous pressure gradient (HVPG) is the gold standard measurement:
- HVPG ≥6 mmHg: portal hypertension
- HVPG ≥10 mmHg: clinically significant portal hypertension (CSPH) — risk of varices and decompensation
- HVPG ≥12 mmHg: risk of variceal hemorrhage
Ascites
Ascites is the most common complication of cirrhosis, occurring in ~50% of patients within 10 years of diagnosis. Pathophysiology: splanchnic vasodilation → decreased effective circulating volume → sodium and water retention.
Diagnosis: Serum-Ascites Albumin Gradient (SAAG) ≥1.1 g/dL confirms portal hypertension as the cause.
Management: Sodium restriction (2g/day), diuretics (spironolactone ± furosemide), large-volume paracentesis with albumin infusion for refractory cases, TIPS for refractory ascites.
Spontaneous Bacterial Peritonitis (SBP)
Life-threatening infection of ascitic fluid without an intra-abdominal source. Must be excluded in any cirrhotic patient presenting with fever, abdominal pain, encephalopathy, or clinical deterioration.
Diagnosis: Ascitic fluid PMN count ≥250 cells/mm³. Treat empirically — do not wait for culture results.
Treatment: IV cefotaxime or ceftriaxone × 5 days + IV albumin on day 1 and 3 (reduces risk of hepatorenal syndrome).
Secondary prophylaxis: Oral norfloxacin or ciprofloxacin indefinitely after first episode.
Gastroesophageal Varices
Portosystemic collaterals that form when HVPG exceeds 10 mmHg. Variceal hemorrhage is the most immediately life-threatening complication of portal hypertension.
Primary prophylaxis: Non-selective beta-blockers (propranolol, carvedilol) or endoscopic variceal ligation (EVL) for medium/large varices.
Acute variceal hemorrhage management:
- Airway protection, resuscitation (restrictive transfusion strategy — target Hgb 7-8 g/dL)
- Vasoactive agents: octreotide IV for 3–5 days
- Antibiotics: ceftriaxone × 7 days (reduces infection and re-bleeding)
- Urgent upper endoscopy within 12 hours: EVL is preferred
- TIPS if endoscopic therapy fails
Hepatic Encephalopathy (HE)
Neuropsychiatric dysfunction caused by accumulation of neurotoxins (primarily ammonia) due to impaired hepatic detoxification and portosystemic shunting.
West Haven Grading: Grade 1 (mild confusion, sleep disturbance) → Grade 4 (coma). Covert HE (Grade 0-1) is common and under-recognized.
Precipitants (find and treat): infection/SBP, GI bleeding, dehydration, constipation, electrolyte disturbance, medications (benzodiazepines, narcotics), renal failure, dietary protein excess.
Treatment: Lactulose (targets colon pH and ammonia absorption), rifaximin (gut-selective antibiotic; reduces recurrence), identify and treat precipitants.
Hepatorenal Syndrome (HRS)
Functional renal failure in the setting of advanced liver disease and portal hypertension, in the absence of parenchymal kidney disease. Diagnosis of exclusion — first exclude hypovolemia and nephrotoxins.
- HRS-AKI (formerly type 1): Rapid progression. Median survival without treatment: weeks.
- HRS-CKD (formerly type 2): Slower progression, often associated with refractory ascites.
Treatment: Norepinephrine or vasoconstrictors (terlipressin where available) + IV albumin. Liver transplantation is definitive therapy.
Hepatocellular Carcinoma (HCC) Surveillance
All patients with cirrhosis should undergo HCC surveillance with liver ultrasound ± AFP every 6 months. HCC is the most rapidly rising cause of cancer mortality in the US, and cirrhosis is present in ~80% of cases.
Early detection changes outcomes: transplant-eligible or resection-eligible HCC has excellent long-term survival. Late detection means palliative intent.